# Cell therapy using neurodegenerative disease modifying molecules (NDMMs) as a means to modulate oxidative damage and neuronal survival in ALS

> **NIH NIH R21** · DARTMOUTH COLLEGE · 2020 · $451,000

## Abstract

The development of fatal paralysis in amyotrophic lateral sclerosis (ALS) is caused by the progressive
degeneration of motor neurons in the central nervous system (CNS). Inhibiting the persistent and toxic
neuroinflammation and oxidative damage around motor neurons is a promising pharmacological strategy to
prevent disease progression. Conventional anti-inflammatory drugs have limited CNS activity and have not been
effective in ALS to date. Regulatory T cells (Tregs) are a subset of lymphocytes with inherent anti-inflammatory
activity, are capable of penetration into the CNS, and higher numbers of Tregs are associated with slower
disease progression in ALS patients. In this proposal, we aim to demonstrate that we can create a treatment that
engages multiple mechanisms to treat ALS using gene-enhanced Tregs to deliver multiple therapeutic activities.
We will use two classes of therapeutic genes that encode what we refer to as neurodegenerative disease
modifying molecules (NDMMs). These genes provide enhanced therapeutic activity to Tregs, and this study is a
way to demonstrate that gene-enhanced T cell therapy is a way to provide additional therapeutic activity in the
CNS at the site of disease. We will test both secreted neuronal growth factors and proteins that prevent anti-oxidative damage. The objective of this proposed research is to test the hypothesize that NDMM-expressing
Tregs will have enhanced therapeutic effects and prevent the death of neurons in ALS models. This proof-of-concept study will allow other NDMM-like molecules to be explored to modulate additional neuron survival or
immunomodulatory pathways. A potential therapeutic breakthrough with therapeutic CAR Tregs would have a
major impact on patients, their families, and clinical management of ALS.

## Key facts

- **NIH application ID:** 10038210
- **Project number:** 1R21NS117895-01
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Charles L. Sentman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $451,000
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10038210

## Citation

> US National Institutes of Health, RePORTER application 10038210, Cell therapy using neurodegenerative disease modifying molecules (NDMMs) as a means to modulate oxidative damage and neuronal survival in ALS (1R21NS117895-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10038210. Licensed CC0.

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